Understanding Molecular Pathways In Non-Responding Dry Eye Disease And Its Therapeutic Intervention
Published 2025 - 43rd Congress of the ESCRS
Reference: FP27.07 | Type: Free paper | DOI: 10.82333/1jej-0y52
Authors: Johannes Birtel* 1 , Haidy Soliman 2 , Ghada Atta 3 , Sarah Schimansky 2 , Akanksha Bagchi 4 , Sjoerd Elferink 5 , Johnson Yan Ning Neo 6 , Peter Charbel Issa 7 , Oliver Findl 8
1Department of Ophthalmology, University Medical Center Hamburg-Eppendorf,Hamburg,Germany, 2University Hospitals Bristol and Weston NHS Foundation Trust,Bristol,United Kingdom, 3Department of Ophthalmology, University of Cologne,Cologne,Germany, 4Moorfields Eye Hospital NHS Foundation Trust,London,United Kingdom;Epsom and St Helier NHS Trust,London,United Kingdom, 5Flevoziekenhuis,Almere,Netherlands, 6Moorfields Eye Hospital NHS Foundation Trust,London,United Kingdom;Whipps Cross University Hospital, Barts Health NHS Trust,London,United Kingdom, 7Department of Ophthalmology, Technical University of Munich, School of Medicine and Health, TUM University Hospital,Munich,Germany, 8Vienna Institute for Research in Ocular Surgery, a Karl Landsteiner Institute, Hanusch Hospital,Vienna,Austria
Purpose
Around 344 million people worldwide have dry eye disease (DED), and 25-30% are treatment non-responders. We aim to identify and treat specific biomarkers
implicated in non-responding Dry eye disease(NR-DED) by using a clinic deployable, customized BMP kit(Bio-M-Pathfinder) and to study clinical and molecular outcomes of targeted biomarker therapy.
Setting
Prospective study conducted at a tertiary ophthalmology center.
Methods
1250 DED patients were seen in our clinic from April- December 2022. Based on signs, symptoms and type of DED, specific treatment was given. At 6 months,1027
patients responded to primary therapy, but 223 didn’t respond and were labelled as NR-DED. Selected biomarkers (MMP-9, IL-6, IL-1b, I-CAM-1, IL-10, IL-17a, TNF-α) were analyzed from tear samples using a customized BMP kit. Artificial intelligence (AI) is used to generate a DED database to identify elevated biomarkers and to start specific targeted therapy against these biomarkers based on their severity. Reassessment of clinical findings, patient satisfaction, quality of life and biomarker levels was done after 6 months of therapy.
Results
Out of 223 NR-DED patients, 60% of eyes demonstrated high levels of MMP-9. Of these, 12% had 1-fold rise, 18% had 2-fold rise and 30% had 3-fold rise in MMP-9.
Eyes with 1-fold rise received immunomodulator therapy. Those with 2-fold rise or higher, received combined vector pulsation/intense pulsed light therapy along with
immunomodulators. 10% of eyes had high levels of ICAM-1, and were given lifitegrast. 20% of eyes had high TNF-α and IL-17a, and were treated with steroids and lubricants. Post-biomarker-specific treatment, 97% of NR-DED eyes had a significant reduction in symptoms and signs, lesser levels of targeted biomarkers, shorter drug response time and lower treatment failure rate.
Conclusions
Conventional therapy of DED includes the prescription of non-specific medication that often leads to NR-DED. A streamlined approach is enabled by customizing treatment to aberrant biomarkers. This would not only permit more economical management by avoidance of multidrug therapy, but also enable monitoring drug response and quantifying results.